VOLUME 35, ISSUE 1

It feels like they’re everywhere – popup ads and TV commercials with snappy jingles for the newest medication, complete with smiling patients, catchy tradenames, and announcers going over side effects at a blistering speed. A relatively new prescription medication risankizumab (Skyrizi) has been advertised heavily ever since its approval in January 2022 by the U.S. Food and Drug Administration for the treatment of adults with active psoriatic arthritis.1

Previously approved for moderate-to-severe plaque psoriasis in April 2019, this new indication broadened the market for risankizumab, and marked the third anti-interleukin 23 (IL23) inhibitor to become commercially available for psoriatic arthritis. Both of the other IL23 inhibitor medications – ustekinumab (Stelara) and guelkumab (Tremfya) – have similarly been the subject of intensive advertising campaigns.2 All of these drugs are monoclonal antibody drugs (also commonly referred to as “biologics”) that target specific antigens and are named using the conventional “MAB” (acronym for monoclonal antibody) suffix.

Risankizumab binds to a subunit of the IL23 cytokine, which is known to be essential in regulating the inflammation that results from infections or chronic autoimmune conditions through the effects of IL23 on interleukin 17 and TNF-alpha. Together, these cytokines work to keep immune cells in an inflammatory state.3 By blocking IL23, risankizumab and other similar IL23 inhibitors reduce inflammation, which in turn reduces psoriatic plaques and arthritis symptoms, with the ultimate goal being remission of the disease entirely. Furthermore, it has a convenient dosing schedule, as patients undergo induction via an initial injection followed by a second subcutaneous injection one month later, then every 12 weeks after that for maintenance.4

One of the downsides of the immunosuppression induced by these medications is susceptibility to infection. Upper respiratory and tineal infections are the most common and, in trials of patients on risankizumab specifically, they experienced a higher rate of infection (22.1%) than patients given a placebo (14.7%).3 It is this characteristic that causes the most consternation about patients on this medication and surgical procedures.

There are currently no comprehensive published guidelines for perioperative management of these IL23 inhibitors, as they are too new. However, there is consensus opinion that risankizumab, just like the other IL23 antibodies, can be continued through low risk surgical procedures that do not result in a break in sterile technique during which the respiratory, gastrointestinal, and genitourinary tracts are not entered.1,6 Examples of this would include dermatologic procedures, ophthalmologic surgeries, or a biopsy of the breast to name a few.6

While orthopedic surgeries and joint replacements are also considered low risk for infection, the American College of Rheumatology (ACR) and the American Association of Hip and Knee Surgeons (AAHKS) published a new set of guidelines in 2022 for the perioperative management of biologics, which included the addition of the newest ones now on the market. They recommended, in general, to hold biologic immunosuppressants in patients with all forms of inflammatory arthritis for their next dosing cycle, and to proceed to schedule surgery after the dose is due. For risankizumab, that would mean scheduling surgery at 12-13 weeks after their last dose.7,8

It becomes trickier when discussing moderate and high-risk surgeries. Surgeries considered moderate risk include those of the genitourinary tract where contamination is not present, sterile abdominal or thoracic surgeries, and head and neck surgeries, while high-risk surgery can be defined to include procedures where the infection risk is greater, such as where there are breaks in sterile technique, spillage from the GI tract, pre-exiting active infection, or devitalized tissue. This would also include emergency surgeries or more complicated surgical procedures from the moderate risk group.6,9 There are some recommendations for a patient to hold their next dose of a biologic and be scheduled after that, just as with the joint replacement recommendations. Many guidelines recommend holding biologics for the longer of either three to five half-lives of the medication or the dosing interval. For, with its 29 day half-life, the longer of the two would still be the 12 week dosing interval.10

Other agencies, such as the British Association of Dermatologists (BAD), note that there are few studies of the efficacy of stopping IL23 inhibitor therapy for surgery, nor studies of the effect that continuing IL23 antibody treatment has on post-operative infections and wound healing. Many of the opinions about perioperative management of these biologics are extrapolated from studying similar drugs in patients with inflammatory bowel disease or rheumatoid arthritis.9

Stopping risankizumab, and other biologics, carries a significant risk of a flare-up in the patient’s psoriasis or psoriatic arthritis. These flare-ups may be managed with short term steroid use, which may also have implications in related to post-operative wound healing. A study of rheumatoid arthritis patients noted that those who stopped their biologic for a procedure were three times more likely to have an acute flare-up of their disease within the next 12 months, but also noted that half of patients had no significant issues related to their rheumatoid arthritis while off their medication.10

In the intraoperative setting, there are no known interactions between any of the IL23 cytokine antibodies and any medications commonly used in the practice of anesthesiology.7

On the post-operative side, patients should be monitored more closely for signs of infection, and the medication should not be restarted until adequate wound healing is demonstrated and all sutures and / or staples have been removed.11

Ultimately, the surgeon or proceduralist is going to have to take a proactive approach for elective moderate and high-risk surgeries, calculating the tolerance of increased infection risk. They will then have to coordinate with the prescribing physician and the patient on potentially holding the next dose, on the proper timing of the procedure related to the previous dose, and on timing to resume the medication if it was held.11 This may result in lengthy wait times for elective surgeries in this cohort of patients.

It should be noted that while risankizumab is currently approved for psoriatic plaque and psoriatic arthritis, there are several phase 3 studies underway of it in the treatment of ulcerative colitis and Crohn’s disease.12 Given the usage of other biologic therapies in inflammatory bowel disease, it is not a stretch to think that there could be an expansion of the indications for risankizumab and other similar biologics, resulting in more patients for which timing of the discontinuation of these medications becomes a consideration in the planning of surgeries and procedures.